Study of BN301, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

NCT05611853 | Terminated Phase 1

• 1 other identifier: BN301-101
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief Summary

Phase 1/2 trial to study the safety, pharmacokinetics and preliminary efficacy of BN301 given intravenously every 3 weeks.

Conditions

B-cell Lymphoma; Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0.3

  Safety and tolerability

  12 months

• Objective Response Rate of participants as assessed by the Lugano 2014 criteria.

  Efficacy

  2 years

Secondary Outcomes (5)

• Maximum concentration (Cmax)

  12 months

• Time to maximum concentration (Tmax)

  12 months

• Elimination half-life (t1/2)

  12 months

• Area under the plasma concentration-time curve (AUC0-t)

  12 months

• CD74 expression

  12 months

Study Arms (3)

3.5mg/kg

EXPERIMENTAL

Will be administered by intravenous infusion every 3 weeks on D1

Drug: BN301

4.2mg/kg

EXPERIMENTAL

Will be administered by intravenous infusion every 3 weeks on D1

Drug: BN301

5.0mg/kg

EXPERIMENTAL

Will be administered by intravenous infusion every 3 weeks on D1

Drug: BN301

Interventions

BN301 DRUG

BN301 will be administered intravenously on Day 1 of every 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent, loss to follow-up, death, or other conditions in which patients are not suitable for study treatment, whichever occurs first. Since this is the first time BN301 will be used in Chinese patients, it is planned to enroll 1 subject at the first dose level of 3.5 mg/kg.

Also known as: STRO-001

3.5mg/kg; 4.2mg/kg; 5.0mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have been fully informed about the study and have voluntarily signed the ICF;
• Age ≥ 18 years;
• Histologically confirmed as B-cell NHL (pathology report), including DLBCL, FL, MZL, and MCL, etc., and the disease requires further treatment;
• Have relapsed/refractory disease or intolerance to prior therapy after ≥ 2 prior lines of therapy including anti-CD20 antibody-containing chemotherapy regimens (e.g., R-CHOP, etc.) (see Section 3.1 for specific definitions);
• At least 1 radiographically measurable lesion (≥ 1 lymph node lesion with longest diameter of \> 1.5 cm, and/or extranodal lesion with longest diameter of \>1.0 cm, as assessed by computed tomography \[CT\]), and no prior radiotherapy on the lesion (evidence of unequivocal progression is required if the lesion has received prior radiotherapy);
• ECOG score 0-2;
• Adequate hematological status (supportive care such as growth factor, platelet transfusion or blood transfusion or correction with drugs are not allowed within 5 days prior to screening):
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L Platelets ≥ 75 × 109/L Hemoglobin ≥ 9 g/dL Note: In Phase 2, if the investigator believes that the above values below the lower limit of the protocol are due to bone marrow involvement by lymphoma, the patient could be enrolled after consultation between investigator and the Sponsor and obtaining written consent from the Sponsor;
• Adequate hepatic, renal, and cardiac functions, defined as:
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• × upper limit of normal (ULN); Total bilirubin ≤ 1.5 × ULN, total bilirubin ≤ 3 × ULN for patients with Gilbert's disease; Creatinine clearance ≥ 50 mL/min as estimated by the Cockcroft-Gault f formula (if \< 50 mL/min, e.g., creatinine ≤ 130 μmol/L is also allowed); Left ventricular ejection fraction ≥ 45%; Note: In Phase 2, the criteria for ALT or AST may be relaxed to ≤ 5 × ULN if the investigator assesses that the increase in ALT or AST is due to liver invasion by lymphoma;
• Male or female patients of childbearing potential must agree to use effective methods of contraception, such as double barrier methods of contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc., during the study and within 90 days after the last dose of study drug. Postmenopausal women (\> 45 years of age and menopause for more than 1 year) and surgically sterilized women are not subject to this condition.

You may not qualify if:

• Chronic lymphocytic leukemia and T-cell malignancies;
• Primary central nervous system lymphoma or lymphoma involving the central nervous system;
• Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV antibody positive). Subjects with occult or pre-hepatitis B infection (defined as HBcAb positive, HBsAg negative) could be enrolled if HBV DNA test result is negative, and subjects with serologically positive HCV antibody, such as negative HCV RNA test result, could also be enrolled;
• Known human immunodeficiency virus (HIV) infection;
• Concomitant clinically significant active infections requiring systemic treatment, including but not limited to chronic kidney infection, chronic chest infection with bronchiectasis and tuberculosis, etc.;
• Expected survival of no more than 24 weeks as judged by the investigator;
• Previous solid organ transplant; autologous hematopoietic stem cell transplant, allogeneic hematopoietic stem cell transplant, or chimeric antigen receptor T-cell (CAR-T) therapy within 60 days prior to enrollment, or had the following conditions:
• Active graft versus host disease (GVHD);
• Cytopenia due to unrecovered hematopoiesis after transplantation;
• Anti-cytokine therapy (e.g., tocilizumab, glucocorticoids) is still required due to CAR-T cell treatment toxicity, or neurological toxicity is \> Grade 1 after CAR-T cell therapy;
• Continuous use of immunosuppressive therapy;
• Pregnant (positive pregnancy test at screening) or lactating female patients;
• QTcF \> 450 msec in male patients or QTcF \> 470 msec in female patients or other significant ECG abnormalities as judged by the investigator;
• Toxicities due to prior anti-lymphoma therapy have not stabilized and have not recovered to ≤ Grade 1 (except for clinically insignificant toxicities such as alopecia, etc.);
• Other malignancies in the past 5 years, with the exception of radically treated basal cell carcinoma of skin, breast cancer in situ and cervix carcinoma in situ;

Sponsors & Collaborators

• BioNova Pharmaceuticals (Shanghai) LTD.: lead

Study Sites (6)

The first affiliated hospital, Zhejiang Unviersity school of medicine

Hangzhou, China

Location

The First Affiliated School of Guangxi Medical University

Nanning, China

Location

Shanghai Jiao Tong University School of Medicine, Ruijin Hospital

Shanghai, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, China

Location

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

Location

Henan Oncology Hospital

Zhengzhou, China

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Weili Zhao, Prof.

  Shanghai Jiaotong University school of Medicine, Ruijin Hospital

  PRINCIPAL INVESTIGATOR

• Liling Zhang, Prof.

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Jie Jin, Prof.

  The first affiliated hospital, Zhejiang Unviersity school of medicine

  PRINCIPAL INVESTIGATOR

• Zhenfang Liu, Prof.

  The First Affiliated School of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

• Baijun Fang, Prof.

  Henan Oncology Hospital

  PRINCIPAL INVESTIGATOR

• Zhengming Jin, Prof.

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: November 10, 2022
• Study Start: November 25, 2022
• Primary Completion: December 25, 2023
• Study Completion: December 25, 2023
• Last Updated: February 21, 2024

Record last verified: 2024-02

Locations

CN (6)